At a glance
At least 24.5 percent of former NFL players who died between 2016 and 2021 had CTE pathology at death, according to a new study.
The authors say the rate could be as high as 97.7 percent, depending on how many players whose brains were not examined also had the disease.
Among 315 brain donors whose tissue showed CTE, 61.3 percent had dementia diagnosed by study clinicians. That number rose to 90.4 percent for donors with Stage IV CTE.
Because CTE can be confirmed only after death, the study cannot determine how common it is among living players.
The findings support continued research on prevention, symptom treatment, and efforts toward new treatments for CTE.
A study of postmortem brain tissue donated by 338 former NFL players reveals that at least 24.5 percent of those who died between 2016 and 2021 had chronic traumatic encephalopathy (CTE)-related brain changes, according to a team led by Boston University, Harvard Medical School researchers at Spaulding Rehabilitation Hospital, and the Concussion and CTE Foundation.
The authors say the rate could be as high as 97.7 percent, depending on how many players whose brains were not examined after death also had the disease.
The results, published Aug. 25 in The BMJ, refine estimates of the prevalence of the degenerative brain condition in this group, placing it far higher than rates in the general population.
“Community brain bank studies have shown that CTE affects less than 1 percent of the general population,” explained lead and corresponding author Daniel Daneshvar, chair of physical medicine and rehabilitation at Mass General Brigham. “To find that somewhere between 24.5 percent and 97.7 percent of NFL players from that time period had this progressive brain disease is a wake-up call for the NFL and scientific communities.”
The researchers also found that dementia was common among the study’s brain donors. Among 315 donors with CTE, 193, or 61.3 percent, had dementia diagnosed by study clinicians based on medical records and informant reports. That number rose to 90.4 percent for donors with the most severe form of CTE, known as Stage IV.
The findings support continued research on prevention, symptom treatment, and efforts to develop treatments for people presumed to have CTE.
Estimating disease without direct measurement
Because CTE can currently be confirmed only through examination of brain tissue after death, researchers cannot directly measure its prevalence in living people. In addition, brain-donor studies may overrepresent individuals with symptoms, since families may be more likely to donate the brain of a player who showed cognitive or behavioral decline.
To address this, the researchers compared a complete list of all former NFL players who died during the full study period — from 2008 to 2021 — against the smaller set whose brains were donated and examined. This allowed them to calculate a defensible range, rather than a single, potentially biased estimate, for CTE prevalence.
Over the full study period, 1,712 former NFL players died, 338 of whom donated their brains. Of those, 315 (93.2 percent) showed CTE pathology — yielding a possible prevalence range of 18.5 percent to 98.7 percent.
The researchers highlighted the narrower 2016-2021 window as their headline estimate (24.5 percent to 97.7 percent) because brain donation was both more frequent and more representative of all deaths during those years. Within that period, 235 players’ brains were donated, and 215 showed signs of CTE.
Neuropathologists who examined the donated brain tissue were kept unaware of each player’s clinical and playing history, and clinicians who diagnosed dementia from medical records and interviews were kept unaware of the pathology findings, so that neither assessment could influence the other.
The findings do not determine how common CTE is among living players, nor do they show that CTE alone caused dementia. Other neurodegenerative and vascular diseases were also common among donors. Even among those whose sole neurodegenerative finding was CTE, only about half had dementia — underscoring that CTE pathology does not always produce clinical symptoms.
Study sites
Most brains were donated to the UNITE Brain Bank at the Boston University CTE Center, with additional donations from Mount Sinai Health System and the UCSF Alzheimer’s Disease Research Center.
The study also included collaborators from across Mass General Brigham; the University of California, San Francisco; Mount Sinai; the U.S. Department of Veterans Affairs; and other institutions.
The research is not affiliated with the Football Players Health Study at Harvard University.
Dementia and CTE severity
The study found that 202 of the 338 donors (59.8 percent) had clinician-diagnosed dementia, and 193 of those (95.5 percent) had CTE pathology. The most severe form of CTE, Stage IV, was associated with a 44 percent higher risk of dementia and with greater impairment in cognition and daily functioning, after adjustment for age and other available factors.
Because brain donors differed from non-donors — donors had significantly longer NFL careers, more Pro Bowl selections, and higher Hall of Fame rates — researchers used a statistical adjustment, known as inverse probability weighting, to make the donor group more representative of all deceased players when estimating this link.
The team also found that less than half of donors with clinician-diagnosed dementia (40.6 percent) had dementia or a related neurodegenerative disease listed as a cause of death on their death certificate. This suggests that studies relying solely on death certificates may significantly underestimate dementia’s burden in this population, the authors said.
“We recognize that these findings will be concerning for NFL players and their families, and we want them to know that help is available,” said senior author Jesse Mez, associate professor of neurology at the BU Chobanian & Avedisian School of Medicine and co-director of clinical research at the BU CTE Center. “We have treatments for many symptoms believed to be associated with CTE, and in our clinic we find that symptoms can improve with proper medical care.”
Because NFL players represent one of the most extreme examples of cumulative exposure to repetitive head impacts, the authors caution that these findings should not be generalized to athletes at other levels of football or in other contact sports without further study. They also note that future research should examine more recently retired players, and that prevention efforts should target cumulative, repetitive head impacts alongside proper concussion management.
Resources for players
The authors say that current or former NFL players concerned about their brain health should consider being evaluated by a clinician who specializes in these conditions. Many health issues can mimic neurodegenerative disease, and many are treatable. While it’s not always possible to eliminate long-term risk, identifying and addressing modifiable risk factors can support brain health and improve quality of life.
For guidance, help finding a specialist, or support in managing health, resources are available through The Trust Powered by the NFL Players Association (NFLPA), the NFLPA’s Professional Athletes Foundation, and the Concussion & CTE Foundation HelpLine.
Adapted from a Mass General Brigham news release.
This research was not associated with the Football Players Health Study at Harvard University. For more information on that study’s activities, recent results, and health resources, visit footballplayershealth.harvard.edu.
Authorship, funding, disclosures
Daneshvar is also HMS associate professor of physical medicine and rehabilitation at Spaulding. Additional authors include Christopher J. Nowinski, Bobak Abdolmohammadi, Charlotte B. Luster, Madeline Uretsky, Brett M. Martin, Joseph N. Palmisano, Jennifer Weuve, Michael D. McClean, Jonathan D. Cherry, Brigid Dwyer, Evan D. Feigel, Michael J. Mastrodicasa, Victor E. Alvarez, Gil D. Rabinovici, William W. Seeley, Lea T. Grinberg, John F. Crary, Thor D. Stein, Lee Goldstein, Douglas I. Katz, Ross D. Zafonte, Yorghos Tripodis, Robert C. Cantu, Robert A. Stern, Michael L. Alosco, and Ann C. McKee.
This work was supported by the National Institute of Neurological Disorders and Stroke and the National Institute on Aging of the National Institutes of Health (grants U54NS115266, U01NS086659, P30AG13846, and P30AG072978) and the Maloney/Carpenter Trauma-Related Neurodegenerative Disease Research Fund.
Several authors disclosed relationships with the NFL Players Association (NFLPA); the Football Players Health Study funded by the NFLPA; the Brain and Body Program funded by the NFLPA; the Mackey-White Committee of the NFLPA; the NFL Concussion Settlement; the NFL Head, Neck, and Spine Committee; and the Concussion Legacy Foundation. Additional disclosures can be found in the paper.
